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Antifungals in systemic neonatal candidiasis
Daniel A C Frattarelli1, Michael D Reed, George P Giacoia
1Division of Clinical Pharmacology, Children's Hospital of Michigan, Wayne State University School of Medicine, 3901 Beaubien, Detroit, MI 48201, USA. dfrattar@med.wayne.edu
Drugs
|April 23, 2004
Summary
Limited data exist for neonatal antifungal treatments, necessitating further research to optimize drug dosing, efficacy, and safety for premature infants and newborns with fungal infections.
Area of Science:
- Neonatal pharmacology
- Infectious diseases
- Pediatric medicine
Background:
- Fungal infections pose significant risks of morbidity and mortality in neonates, particularly premature infants.
- Current treatments include polyene macrolides, azoles, and fluorinated pyrimidines, with echinocandins showing emerging promise.
- Existing pharmacokinetic and efficacy data for neonatal antifungals are often limited, derived from small studies or adult data.
Purpose of the Study:
- To review the current understanding of antifungal drug pharmacokinetics, efficacy, and toxicity in neonates.
- To identify gaps in knowledge regarding optimal dosing and treatment duration for systemic fungal infections in this population.
- To highlight the need for further research to improve antifungal therapy in neonates.
Main Methods:
- Literature review of pharmacokinetic and efficacy data for commonly used neonatal antifungals.
- Analysis of available data on amphotericin B (deoxycholate and lipid formulations), fluconazole, and flucytosine in neonates.
- Examination of toxicity profiles reported for these antifungal agents in the neonatal population.
Main Results:
- Pharmacokinetic data are scarce and variable for amphotericin B deoxycholate and flucytosine; limited data exist for lipid formulations of amphotericin B.
- Fluconazole has the most available neonatal pharmacokinetic data, showing less variability.
- Efficacy data are largely from retrospective studies; while supporting use, they do not define optimal dosing or duration.
- Amphotericin B deoxycholate exhibits nephrotoxicity and electrolyte abnormalities; lipid formulations show similar toxicity despite higher doses.
- Fluconazole appears to have a milder and less frequent toxicity profile compared to amphotericin B.
Conclusions:
- There is a critical lack of comprehensive data on the pharmacokinetics, optimal dosing, and toxicity of antifungal drugs in neonates.
- Existing data, primarily from retrospective studies, support the use of certain antifungals but cannot establish definitive treatment guidelines.
- Further rigorous studies are essential to optimize antifungal therapy and improve outcomes for neonates with fungal infections.